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Functionally charged nanosize particles differentially activate BV2 microglia.
Citation:
VERONESI, B., L. Liu, S. D. HESTER, W. O. WARD, J. Tajuba, M. POOLER, C. SWARTZ, N. Saleh, G. V. LOWRY, AND S. Simon. Functionally charged nanosize particles differentially activate BV2 microglia. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
To examine the effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) .
Description:
The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Nanosize (860-950 nm) spherical polystyrene microparticles (SPM) were coated with carboxyl (COOH-) or dimethyl amino (CH3)2-N- groups to give a net negative or positive (neutral) charge, respectively. Both SPM stimulated the release of reactive species and inflammatory cytokines, increased caspase 3/7 activity, and reduced intracellular ATP levels. SPM-COOH- produced qualitatively and/or quantitatively greater change in all instances. Confocal and transmission electron microscopy revealed that the SPM were phagocytosed as singlets but formed large intra-cellular micron size aggregates. Microarray analysis indicated that SPM-COOH- and SPM-(CH3)2-N- differentially affected metabolic, transcriptional and oxidative stress pathways. Intracellular calcium increases, measured with Fura-2 ratio imaging, indicated that each SPM stimulated calcium increases through different but unidentified receptors/pathways. Increases in intracellular calcium did not occur in response to conventional TRPV vanilloid receptor agonists (e.g., acid pH, capsaicin) nor were blocked by their antagonists (e.g., capsazepine), indicating that the above cellular changes in BV2 microglia were not mediated by TRPV receptors or pH sensitive channels. Together, these data indicate that cellular and genomic expressions of oxidative stress mediated inflammation are differentially stimulated by the electrostatic surface charge carried on inert nanosize particles. Such data link the physical properties (surface charge) of nanosize particles to their (adverse) biological effects and are relevant to understanding their mode of action. DISCLAIMER: This document has been reviewed by the NHEERL but does not necessarily reflect the views of the Agency.